T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia

Status: Recruiting
Phase: Phase 1
DFCI Protocol ID: 13-526

The purpose of this study is to test the safety of giving the patient special cells made from their own blood called "Modified T-cells". The goal is to find a safe dose of modified T-cells for patients whose leukemia has returned to the bone marrow.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Lewis Silverman, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria for Collection Arm of the protocol:

Age < 26 years, whose disease meets one of the following 3 criteria:

  -  VHR*

  -  Patients in 1st or subsequent marrow relapse (isolated or combined), at the time of
     relapse, during retrieval therapy, or after achievement of CR.

  -  Refractory disease *Definitions of VHR B-ALL include the following:

       -  NCI HR-ALL and age ≥ 13 years at diagnosis

       -  CNS-3 leukemia at diagnosis

       -  Day 29/End of Induction BM MRD > 0.01%

       -  Induction failure (M3 BM at Day 29/End of Induction)

       -  Hypodiploidy (n< 44 chromosomes and/or a DNA index < 0.81)

       -  t(9;22) ALL (Philadelphia Chromosome/Ph+ ALL)

       -  t(17;19) ALL or Ph-Like ALL

       -  MLL gene rearrangement

       -  IKZF1 deletions

       -  Intrachromosomal amplification of chromosome 21 (iAMP21) Please note patients
  that only meet the criteria for collection/storage of PBMCs will need to be
  reconsented prior to infusion of genetically modified T-cells.

Inclusion Criteria for Treatment Arm of this protocol:

  -  Patients must have a history of relapsed/refractory CD19+ B-ALL involving the marrow
     to be eligible for infusion of modified T cells.

  -  Please note ≥5% blasts by morphology, FISH/cytogenetics, molecular translocation
     and/or flow cytometry constitutes a bone marrow relapse on this protocol. Patients
     must also fulfill one of the following criteria to be eligible for infusion of
     modified T cells:

       -  Second or greater (≥2) relapse

       -  Early first marrow relapse (1st CR <18 months)

       -  Intermediate/Late first marrow relapse (1st CR >18 months from 1st CR) with poor
  initial response (≥5% blasts by morphology and/or flow cytometry) following
  reinduction chemotherapy

       -  Refractory Disease

       -  Ineligible for HSCT as determined by the treating physician in consultation with
  the BMT service

       -  Patient would not benefit from additional chemotherapy as determined by the
  treating physician

  -  KPS or Lansky score ≥ 60

  -  Pulmonary function (measured prior to conditioning chemotherapy):

     o > 90% oxygen saturation on room air by pulse oximetry.

  -  Renal Function (measured prior to conditioning chemotherapy):

     o Serum creatinine ≤2.0mg/dL for patients over 18 years or ≤2.5 x institutional ULN
     for age

  -  Hepatic Function (measured prior to conditioning chemotherapy):

       -  AST ≤ 5 x the institutional ULN. Elevation secondary to leukemic involvement is
  not an exclusion criterion. Leukemic involvement will be determined by the
  presence of progressive relapse defined by escalating bone marrow or peripheral
  blood leukemia blasts within the previous month and the absence of initiation of
  know hepatotoxic medication (e.g. azoles).

       -  Total bilirubin ≤ 2.5 x the institutional ULN

Exclusion Criteria for Collection of T cells/PBMCs:

  -  Karnofsky/Lansky performance status <60.

  -  Patients with any concurrent active malignancies as defined by malignancies requiring
     any therapy other than expectant observation

  -  Patients with active HIV, hepatitis B or hepatitis C infection.

  -  Females who are pregnant

Exclusion Criteria for Treatment:

  -  Karnofsky/Lansky performance status <60.

  -  Patients with any concurrent active malignancies as defined by malignancies requiring
     any therapy other than expectant observation

  -  Patients will be excluded if they have isolated extra-medullary relapse of ALL

  -  Females who are pregnant.

  -  Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD
     or an overt autoimmune disease (e.g. hemolytic anemia) following allo-HSCT requiring
     glucocorticosteroid treatment (>0.5 mg/kg/day prednisone or its equivalent) as
     treatment.

  -  Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic
     evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia
     (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28
     days of treatment. Prophylactic intrathecal medication is not a reason for exclusion.

       -  If the LP is traumatic (containing RBCs) and cannot be repeated the
  Steinherz/Bleyer ratio will be used to determined unequivocal evidence of CSF
  leukemia at the discretion of the treating physician.

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